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Positron emission tomographic scan

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POSITRON EMISSION TOMOGRAPHY SCAN Moderator : Dr Sanjay Pandey Presenter : Prashant Makhija
  • 1. POSITRON EMISSION TOMOGRAPHY SCANModerator : Dr Sanjay Pandey Presenter : Prashant Makhija

2. PET Scan What it is ? Historical background How does it work ? Applications in Neurology Dementia Epilepsy Movement disorders Stroke Brain tumors Others Limitations Potential future applications 3. What it is ? A scanning procedure that enables visualisation of the bodys metabolic activity by employing positron- emitting radioactive isotopes PET Scanner noninvasively generates 3D images of the distribution of an IV administered radiopharmaceutical within the body Images enable evaluation of physiological phenomena that include Glucose metabolism Oxygen metabolism Cerebral blood flow Receptor sites in brain 4. History Of PET Scan- The Milestones Ernest O. Lawrence (early1930s) ,University of California, at Berkley laboratory invented the cyclotron In 1953,Gordon Brownell at MIT created a precursor to the up coming PET scanner PC I was the first tomographic imaging device , designed in 1968 , completed in 1969 and reported in 1972 Subsequently PC-II and its commercial version were developed In the early 1970s , the researches realized role of PET in assessing human brain function and the most favored technique was blood flow measurement with radiopharmaceutical, O-15 water 5. History Of PET Scan- The Milestones contd Louis Sokoloff and colleagues, and Al Wolf and Joanna Fowler (1976), developed fluorodeoxyglucose with Fluorine-18 (FDG)expanding the scope of PET imaging James Robertson(1973) proposed the ring system in PET scanning which produced high resolution images without motion ( PCR-I & PCR-II) In the year 2000, David Townsend (physicist at the University of Geneva ,Switzerland) , and Ronald Nutt, electrical engineer ,introduced the PET/CT scanner, fusion of a state-of-the-art PET scanner and a fast, multidetector spiral CT scanner The PET/CT scanner featured in Time magazine that year as Invention of the Year 6. History Of PET Scan- The Milestones contd 7. How does it work ? A positron-emitting radioisotope is administered intravenously Radiopharmaceutical gets distributed through the body via blood circulation, accumulating in the organs or body systems being studied Radioisotope decays, emitting positrons A positron (e+), the antimatter equivalent of an electron, collides with one of the nearby electrons (e-) ANNIHILATION Results in a burst of electromagnetic energy - two 511-keV gamma rays 180 degrees apart 8. PET scanner detects the gamma rays using detectors The scanner electronics determine which of the gamma rays are coincident and pairs them into coincident events COINCIDENCE is determined by employing a time frame or coincidence window- if two coincident gamma rays are detected on opposite sides of the patients body within nanoseconds of each other, the computer pairs and records them into coincident events PET scanner collects all coincident events and sorts them into a sinogram Sinogram is reconstructed with corrections by the computer to produce two- or three-dimensional images 9. Common PET radioisotope tracers & their Application Radioisotope tracer usedApplicationC(R)-PK11195Activated microgliaC-MethionineCellular amino acid uptakeC-FlumazenilCentral benzodiazepine bindingH2 150Cerebral blood flowF-6-FlurodopaDopamine storageC-SCH23390Dopamine D1 receptor bindingC-RacloprideDopamine D2 receptor bindingF-2-deoxyglucoseGlucose metabolismCobaltInflammatory responseC-DeprenylMonoamine oxidase A bindingC-DiprenorphineOpiate receptor bindingC-carfentanilOpiate receptor bindingF-cyclofoxyOpiate receptor bindingO2Oxygen metabolism11 11111811 11 1855 11 11111815 10. 1. ROLE IN MOVEMENT DISORDERS PARKINSONS DISEASE Diagnosis of PD in early stages. (FDOPA, can quantify the deficiency of dopamine synthesis and storage within presynaptic striatal nerve terminal.) Heiss WD, Eur J Neurol.2004 Diagnosis of PD in preclinical stages in persons at risk ( Patients with early PD have low- fluorodopa F18 uptake in one putamen with preserved uptake in the caudate nucleus.) Sawle GV, Arch Neurol.1994 Differentiation between PD with other movement disorders 11. Differentiation between PD and striatonigral degeneration by PET (carbon11 labeled SCH23390) (SND patients showed mean 12,21, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients) Shinotoh H, JNNP,1993 Assessment of graft viability after embryonic dopamine cell implantation (a significant increase in FDOPA uptake in the putamen of the group receiving implants was observed ) Nakamura T et al , Ann Neurol. 2001 12. PET Finding in Parkinsonian syndromes PET TracerParkinsons diseasePSPMSACBGDF DopaAsymmetric reductionSymmetrical reductionSymmetrical reductionputamen>caudatecaudate=putamencaudate=putamenAsymmetric & equivalent reduction18caudate=putamen18FDGNormal/raised in Striatum, Reduced in tempoparietal cortexReduced in Bilateral striatum and frontal corticesReduced in striatum, brainstem, and cerebellumAsymmetric reduction in striatum, thalamus, frontal and temporoparietal cortices 13. DYSTONIA 18 FDG-PET studies show a decrease in regional cerebral glucose metabolism in caudate & lentiform nucleus and in the frontal field of the mediodorsal thalamic nucleus Karbe H et al ,Neurology.1992 HUTINGTONS DISEASE Preclinical detection by demonstrating reduced caudate glucose utilisation in persons at high risk for the disorder and thus confirm DNA studies Hayden MR et al, Neurology.1987 14. 2. ROLE IN DEMENTIA Early diagnosis of Alzheimer's disease Shows abnormalities in early stage and may even aid in preclinical diagnosis Is superior to neuropsychological tests Zamrini E, Neurobiol Aging.2004 For screening of AD in high-risk groups of asymptomatic patients( persons homozygous for epsilon 4 allele for apolipoprotien E ) Reiman EM , N Engl J Med.1996 in vivo imaging of amyloid peptide can help in diagnosis of AD in preclinical and prodromal phases Sair III, Neuroradiology.2004 15. Detection of progressive Dementia 18 FDG- PET has a sensitivity of 93% and specificity of 76% in identifying progressive dementia in patients undergoing evaluation for cognitive impairment Silverman DH et al, JAMA. 2001 PET has a sensitivity & specificty of 94% & 73% , respectively in identifying patients with neuropathologically confirmed AD Silverman DH et al, JAMA. 2001 16. Differentiation between AD and Vascular Dementia Mild or atypical cases of AD can be differentiated from VaD using 18FDGPET hypometabolism in temporoparietal & frontal association areas, but relative sparing of primary cortical areas, basal ganglia and cerebellum In VaD, a different pattern characterized by scattered areas with reduction of regional cerebral glucose metabolism extending over cortical and subcortical areas Meilke R et al, J Neural Transm Suppl.1998 17. Differentiation between AD and Dementia with Lewy bodies (DLB) In DLB , regional cerebral glucose metabolism is reduced in temporoparietooccipito association cortices and the cerebellar hemispheres, as against AD, where medial temporal and cingulate are affected Imamura T et al, Neurosci.1997 Monitoring the effect of treatment with cholinesterase inhibitors in AD PET evaluation before and after therapy with Donepezil or Rivastigmine is helpful in assessing the treatment benefits 18. These PET scan images show normal brain activity (left) and reduced brain activity caused by Alzheimer's disease (right). The diminishing of the intense white and yellow areas in the image on the right indicates mild Alzheimer's disease, with the increase of blue and green colors showing decreased brain activity 19. Alzheimers diseaseNormal 20. 3. ROLE IN STROKE Identification of viable penumbra in acute ischemic stroke Flumazenil( 11C) PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke Heiss WD et al, Stroke.2000 Differentiation between recent and old stroke in patients with recuurent ischemic strokes Recently infarcted areas, less than 2-month old, have a high Cobalt(55 Co) uptake ratio, whereas infarcts of 6 months to 1yr have an uptake ratio comparable to normal brain tissue De Reuck et al, Clin Neurol Neurosurg.1999 21. Predicting probability of cortical infarction in acute ischemic stroke FMZ PET carries a lower probability of false positive reaction in comparison to DWI MRI Heis WD et al , Stroke.2004 Prediction of engraftment of neuronal implantation in chronic stroke FDG-PET has been used to map metabolic response to neuronal cell implantation in the human neuroimplantation trial for stroke Meltzer CC et al , Neurosurgery.2001 Demonstration of Diaschisis De Reuck J et al, Acta Neurol Belg.1997 22. 4. ROLE IN BRAIN TUMORS Diagnostic assessment of cerebral gliomas Combined use of fluroethyl-l-tyrosine(FET) PET and MRI has a sensitivity of 93% & speficity of 94% for detection of tumor tissue Pauleit D et al, Brain.2005 Grading of brain tumors FET- PET can differentiate between malignant and benign lesions of the brain High & low grade gliomas exhibit different uptake kinetics of FET Wekesser M et al, Eur J Nucl Med Mol Imaging. 2005 23. Differentiation between tumor recurrence and radiation necrosis 11C-Methionine PET is useful Tsuyuguchi N et al (J Neurosurg, 2003) sensitivity of 77.8% & specificity of 100% Combined use of 11C-Methionine and FDG-PET enhances the accuracy of discrimination Ogawa T et al, Acta Radiol.1991 Higher glucose metabolism in cerebral lymphomas also help to distinguish it from cerebral infections (toxoplasmosis & tuberculomas ) in patients with AIDS O Doherty MJ et al, J Nucl Med. 1997 24. 5. ROLE IN EPILEPSY Presurgical evaluation & localisation of epileptogenic foci epileptogenic focus : decreased glucose metabolism and blood flow interictaly the rates of lesion localisation by MR, ictal SPECT, and interictal FDG-PET was 60%, 70%, & 78% , resp. Hwang SI, Am J Neuroradiol. 2001 obviates the need for invasive electrophysiological monitoring in most instances Cummings TJ, Neurosurg Clin N Am.1995 25. Temporal lobe epilepsy Deuterium-Deprenyl PET helps in identification of the epileptogenic temporal lobe Kumlien E, Epilepsia. 1995 Seizure lateralization with qualitative MR is inferior to qualitative PET Helveston W, Am J Neuroradiol. 1996 Routine diagnosis of epilepsy is more sensitive than MRI Abnormalities of PET are detected in about 40% of those pts who have supposedly normal brain MRI Swartzz BE, Mol Imaging Biol.2002 26. Treatment & outcome Alpha methyl-L-tryptophan(AMT) PET identifies nonresected epileptic cortex in patients with failed neocortical epilepsy surgery Juhasz C , Epilepsia. 2004 Prediction of postoperative outcome FDG-PET interictal metabolic pattern predicts seizure outcome at 2yrs after surgery in pts with medial TLE Dupont S, Arch Neurol.2000 A combination of MR & PET identifies 95% of pts with good outcome post epilepsy surgery Heinz R, Am J Neuroradiol. 1994 27. 6. MISCELLANEOUS HEADACHE increased blood flow in midline brainstem structures during the headache phase, persists even after treatment- reflecting activity of migraine centre Diener HC, Headache. 1997 CHRONIC FATIGUE SYNDROME FDG-PET - hypometabolism in the right mediofrontal cortex & brainstem . Brainstem hypometabolism seems to be a specific marker for in vivo diagnosis of CFS Tirelli U, Am J Med. 1998 28. ENCEPHALITIS Rasmussens encephalitis FDG-PET increases the diagnostic confidence in pts whose MR findings are subtle or distributed bilaterally Fiorella DJ, Am J Neuroradiol. 2001 to study the neuroinflammation in RE in vivo , aid in the selection of appropriate biopsy sites and assess the response to anti-inflammatory therapeutic agents Paraneoplastic encephalitis(PNE) FDG-PET has shown positive findings in a case of PNE , associated with Cystic teratoma, where MR was negative . PET may be superior to MR in some cases of PNE Dadparvar S , Clin Nucl Med. 2003 29. MULTIPLE SCLEROSIS Quantative cerebral abnormalities detected by FDG-PET- marker of disease activity in understanding the pathophysiological expression and therapeutic response of MS Bakshi R, J Neuroimaging. 1998 Cobalt-PET - for assessing the disease progression rate in relapsing progressiveMS Jansen HM, J Neurol Sci. 1995 30. LIMITATIONS Major limitation of PET is lack of availability and cost Technical limitations, relatively high incidence of false-positive reports, reduces its specificity Specially trained personnel are required to interpret the reports Not a good imaging test in isolation Cyclotron is required (for generating radio-isotopes) 31. POTENTIAL FUTURE APPLICATIONS Mainstay of clinical application in neurology is in the domains of Epilepsy surgery and Neuro-oncology Early diagnosis of brain metastasis; distinguishing local recurrences from radiotherapy induced changes; and detecting malignant transformation of low grade tumours Preoperative localisation of seizure foci in potential candidates for epilepsy surgery, especially in those with equivocal MRI findings 32. As an adjunct to clinical diagnosis in atypical cases of parkinsonian syndromes and dementia Early and presymptomatic diagnosis of individuals at risk for neurodegenerative disorders such as AD and PD if an effective neuroprotective agent becomes available In vivo amyloid imaging in AD Prediction of engraftment of neuronal implantation in chronic stroke 33. THANK YOU